Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study.

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age >18 years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 ± 8.3 years, BMI 24.9 ± 3 kg/m2, mean duration of HIV infection of 8.1 ± 5.3 years) were included. Baseline HbA1c was 4.4 ± 0.4% and baseline presence of BactDNA in six patients. After 8.5 ± 0.5 years of follow-up, change in HbA1c was 1.5 ± 0.47% in patients with BactDNA vs 0.87 ± 0.3% in the rest of the sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis.

Biological markers of fertility (inhibin-B) in HIV-infected men: influence of HIV infection and antiretroviral therapy.

OBJECTIVES: Inhibin B (IB) levels and the IB: follicle-stimulating hormone (FSH) ratio (IFR), biomarkers of global Sertoli cell function, show a strong relationship with male fertility. The aim of the study was to examine the prevalence of impaired fertility potential in HIV-infected men and the influence of antiretroviral therapy (ART) on fertility biomarkers. METHODS: A cross-sectional study with sequential sampling was carried out. A total of 169 clinically stable patients in a cohort of HIV-infected men undergoing regular ambulatory assessment in a tertiary hospital were included. The mean [± standard deviation (SD)] age of the patients was 42.6 ± 8.1 years, all were clinically stable, 61.5% had disease classified as Centers for Disease Control and Prevention (CDC) stage A, and were na?ve to ART or had not had any changes to ART for 6 months (91.1%). Morning baseline IB and FSH concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescent immunoassay (ECLIA), respectively. A multivariate logistic regression model was used to identify factors associated with impaired fertility, defined as IB < 119 pg/mL or IFR < 23.5. RESULTS: The mean (± SD) IB level was 250 ± 103 pg/mL, the median [interquartile range (IQR)] FSH concentration was 5.1 (3.3-7.8) UI/L and the median (IQR) IFR was 46.1 (26.3-83.7). The prevalence of impaired fertility was 21.9% [95% confidence interval (CI) 16.3-20.7%]. Negative correlations of body mass index and waist: hip ratio with FSH and IB levels were observed (P < 0.01), while a sedentary lifestyle and previous nevirapine exposure were associated with a decreased risk of IB levels ≤ 25th percentile in multivariate analysis. Only older age, as a risk factor, and sedentary lifestyle, with a protective effect, were independently associated with impaired fertility in multivariate analysis. CONCLUSIONS: Global testicular Sertoli cell function and fertility potential, assessed indirectly through serum IB levels and IB: FSH ratio, appear to be well maintained in HIV-infected men and not damaged by ART.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Valproic acid could help in the fight against COVID-19: A case-control study.

OBJECTIVE: There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. MATERIAL AND METHODS: A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT) (292 days) or at least 20% of the study period (notAT) (≥58 days) and if VPA levels were in therapeutic range (ATR) (50-100mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). RESULTS: During the study period, 6183 PCR+ were detected among 281,035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736% (OR 0.785 (95%CI 0.443-1.390) and 1.910% (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076-3.871). CONCLUSION: Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.

Impact of vitamin D insufficiency on insulin homeostasis and beta cell function in nondiabetic male HIV-infected patients.

OBJECTIVES: Vitamin D is thought to play a role in glucose homeostasis and beta cell function. Our aim was to examine the impact of plasma 25-hydroxyvitamin D [25(OH)D] upon in vivo insulin sensitivity and beta cell function in HIV-infected male patients without diabetes. METHODS: A cross-sectional study was carried out involving a cohort of HIV-infected patients undergoing regular assessment in a tertiary hospital. Eighty-nine patients [mean (± standard deviation) age 42 ± 8 years] were included in the study: 14 patients were antiretroviral therapy (ART)-naïve, while 75 were on ART. Vitamin D insufficiency (VDI) was defined as 25(OH)D < 75 nmol/L; insulin sensitivity was determined using a 2-h continuous infusion of glucose model assessment with homeostasis (CIGMA-HOMA), using the trapezoidal model to calculate the incremental insulin and glucose areas under the curve (AUCins and AUGglu, respectively). Beta cell function was assessed using the disposition index (DI). Abdominal visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) were measured by magnetic resonance imaging (MRI) and 1-H magnetic resonance spectroscopy. Multivariate linear regression analysis was performed. RESULTS: VDI was associated with insulin resistance (IR), as indicated by a higher CIGMA-HOMA index (odds ratio 1.1) [1.01-1.2]. This association was independent of the main confounders, such as age, Centers for Disease Control and Prevention (CDC) stage, ART, lipodystrophy, body mass index, VAT:subcutaneous adipose tissue ratio and HTGC, as confirmed by multivariate analysis (B = 12.3; P = 0.01; r² = 0.7). IR in patients with VDI was compensated by an increase in insulin response. However, beta cell function was lower in the VDI subpopulation (33% decrease in DI). CONCLUSIONS: VDI in nondiabetic HIV-positive male patients is associated with impaired insulin sensitivity and a decrease in pancreatic beta cell function.

Impact of Sepsis Flow Chip, a novelty fast microbiology method, in the treatment of bacteremia caused by Gram-negative bacilli.

OBJECTIVE: The aim of this study was to assess the impact of the information provided by the new Sepsis Chip Flow system (SFC) and other fast microbiological techniques on the selection of the appropriate antimicrobial treatment by the clinical researchers of an antimicrobial stewardship team. METHODS: Two experienced clinical researchers performed the theoretical exercise of independently selecting the treatment for patients diagnosed by bacteremia due to bacilli gram negative (BGN). At first, the clinicians had only available the clinical characteristics of 74 real patients. Sequentially, information regarding the Gram stain, MALDI-TOF, and SFC from Vitro were provided. Initially, the researchers prescribed an antimicrobial therapy based on the clinical data, later these data were complementing with information from microbiological techniques, and the clinicians made their decisions again. RESULTS: The data provided by the Gram stain reduced the number of patients prescribed with combined treatments (for clinician 1, from 23 to 7, and for clinician 2, from 28 to 12), but the use of carbapenems remained constant. In line with this, the data obtained by the MALDI-TOF also decreased the combined treatment, and the use of carbapenems remained unchanged. By contrast, the data on antimicrobial resistance provided by the SFC reduced the carbapenems treatment. CONCLUSIONS: From the theoretical model the Gram stain and the MALDI-TOF results achieved a reduction in the combined treatment. However, the new system tested (SFC), due to the resistance mechanism data provided, not only reduced the combined treatment, it also decreased the prescription of the carbapenems.

Etiology of bloodstream infections at a population level during 2013-2017 in the Autonomous Community of Valencia, Spain.

OBJECTIVE: Bloodstream Infections has become in one of the priorities for the antimicrobial stewardship teams due to their high mortality and morbidity rates. Usually, the first antibiotic treatment for this pathology must be empirical, without microbiology data about the microorganism involved. For this reason, the population studies about the etiology of bacteremia are a key factor to improve the selection of the empirical treatment, because they describe the main microorganisms associated to this pathology in each area, and this data could facilitate the selection of correct antibiotic therapy. METHODS: This study describes the etiology of bloodstream infections in the Southeast of Spain. The etiology of bacteremia was analysed by a retrospective review of all age-ranged patients from every public hospital in the Autonomous Community of Valencia (approximately 5,000,000 inhabitants) for five years. RESULTS: A total of 92,097 isolates were obtained, 44.5% of them were coagulase-negative staphylococci. Enterobacteriales was the most prevalent group and an increase in frequency was observed along the time. Streptococcus spp. were the second microorganisms more frequently isolated. Next, the most prevalent were Staphylococcus aureus and Enterococcus spp., both with a stable incidence along the study. Finally, Pseudomonas aeruginosa was the fifth microorganism more frequently solated. CONCLUSIONS: These data constitute a useful tool that can help in the choice of empirical treatment for bloodstream infections, since the knowledge of local epidemiology is key to prescribe a fast and appropriate antibiotic therapy, aspect capital to improve survival.

Impact of a stewardship program on bacteraemia in adult inpatients.

OBJECTIVE: Bloodstream infections (BSIs) are associated with considerable morbidity and mortality among inpatients. The aim of this study was to evaluate the impact of a stewardship program on clinical and antimicrobial therapy-related outcomes in patients with bacteraemia. METHODS: Single-centre, before-and-after quasi-experimental study in adult inpatients. Over 1 January 2013 to 31 June 2013 all patients aged 18 years or older with a bacteraemia (interven-tion group, N=200) were compared to a historical cohort (1 Janu-ary 2012 to 31 December 2012) (control group, N=200). RESULTS: Following blood culture results and adjusting for potential confounders, the stewardship program was associated with more changes to antibiotic regimens (adjusted odds ratio [ORa]: 4.6, 95% CI 2.9, 7.4), more adjustments to antimicrobial therapy (ORa: 2.4, 95% CI 1.5, 3.8), and better source control in the first five days (ORa 1.6, 95% CI: 1.0, 2.7). In the subgroup that initially received inappropriate empiric treatment (n=138), the intervention was associated with more antibiotic changes (OR: 3.9, 95% CI: 1.8, 8.5) and a better choice of definitive antimicrobial therapy (OR 2.3 95% CI: 1.2, 4.6). There were also more antibiotic changes in the subgroups with both Gram-negative (OR: 2.8, 95% CI: 1.6, 4.9; n=217) and Gram-positive (OR: 4.6, 95% CI: 1.8, 9.9; n=135) bacteraemia among those receiving the intervention, while the Gram-positive subgroup also received more appropriate definitive antimicrobial therapy (OR: 3.9, 95% CI: 1.8, 8.8). CONCLUSIONS: The stewardship program improved treatment of patients with bacteraemia and appropriateness of therapy.

Can alprostadil improve liver failure in HIV-infected patients with severe acute viral hepatitis?

Liver failure with hepatic encephalopathy during an acute viral hepatitis carries a very high mortality. Liver transplantation is the usual treatment, but for poor candidates for transplantation only supportive therapy is available. Two patients with HIV infection developed an acute B hepatitis with liver insufficiency and hepatic encephalopathy. After an alprostadil infusion was begun they improved quickly and made a full recovery. This drug merits further investigation.

Progressive multifocal leukoencephalopathy treated with cidofovir in HIV-infected patients receiving highly active anti-retroviral therapy.

Progressive multifocal leukoencephalopathy (PML) has been a devastating disease for HIV-1-infected patients since the beginning of the AIDS pandemic. Currently, highly active antiretroviral therapy (HAART) seems to improve the outcome of PML in many patients. We describe two cases of PML whose course worsened in spite of HAART, but had a good response to cidofovir.

Clinical presentation of HIV infection in patients aged 50 years or older.

OBJECTIVES: To describe the clinical presentation of HIV disease in older patients. METHODS: In the period 1989-1996 we reviewed the medical records of 100 patients with human immunodeficiency virus (HIV) infection aged 50 years or older and, 197 controls among HIV-infected patients aged 15-40 years, who attended six institutions in the autonomous community of Valencia (Spain). RESULTS: Older patients were mostly males (86%), men who have sex with men (42%) or unknown (20%) as exposure categories. Older patients had lower CD4 cell counts/mm3 (163+/-136 vs. 450+/-373, P= 0.008), and had AIDS at first evaluation (49% vs. 29%, P = 0.0006) compared with younger patients. For patients presenting with AIDS at HIV infection diagnosis, type and frequency of AIDS indicator diseases did not differ between older and younger patients. CONCLUSION: Studies on clues for early detection of HIV infection in patients aged 50 years or older are urgently needed to improve the health care in this population.

Abnormalities in the metabolism of acetaminophen in patients infected with the human immunodeficiency virus (HIV).

The urinary concentration of acetaminophen and its glucuronide, sulphate, cysteine, and mercapturate conjugates was measured by high-performance liquid chromatography in 32 healthy volunteers, 9 untreated symptom-free HIV-seropositive subjects, and 19 patients with AIDS after a single oral dose of 1.5 g of acetaminophen. The concentration of the glucuronide conjugate was significantly lower in AIDS patients when simultaneously compared with concentrations found in healthy individuals and symptoms-free HIV-seropositive subjects. Differences between healthy volunteers and symptom-free HIV seropositives were not encountered. By contrast, urinary concentrations of sulphate and oxidation pathway-derived metabolites were significantly higher in AIDS patients as compared with the other two groups. When AIDS patients treated with zidovudine were compared with those not given this medication, differences in the urinary excretion of acetaminophen and its metabolites were not observed. However, the urinary concentration of mercapturic acid was significantly higher in those given enzyme inducers, such as rifampicin or phenytoin, than in AIDS patients not treated with these drugs. In summary, patients with advanced HIV infection showed reduced acetaminophen glucuronidation and increased formation of the hepatotoxic oxidation metabolites, which was independent of zidovudine therapy.

[A critical analysis of clinical trials in acute pancreatitis published between 1983 and 1989]. / Análisis crítico de los ensayos clínicos en pancreatitis aguda publicados entre 1983 y 1989.

BACKGROUND: The aim of the study was a critical review of recent clinical trials in acute pancreatitis (AP) to draw recommendations for future studies. METHODS: The pharmacological clinical trials in AP reported in English from 1983 to 1989 were identified through a computer assisted Medline search, and a manual review of the references in the initial articles. In addition to the characteristics of the studies, the results on the clinical variables were also recorded. In case of negative results, the power of the study to detect 50% reductions in mortality and complications was also calculated. RESULTS: In the 12 identified studies 10 different drugs were used. Only 58% were double blind. The interval between the onset of symptoms and therapy was not specified in eight studies (67%) and was two days or longer in the rest. In six studies (50%), the duration of treatment was very short (less than three days). Except in two studies, mild forms of AP predominated. Some clinical efficacy of 5-FU, TRH and CaNa2-ED-TA was reported, although with small relevance. In no trial any beneficial effects on mortality or complications were found, although the statistical power was in general low, and therefore a false negative result cannot be excluded. CONCLUSIONS: The guidelines for clinical trials in AP should be unified, particularly regarding the type of study, inclusion criteria and duration of treatments. Some treatments may be too early discarded owing to false negative results due to small sample size.

[The usefulness of different markers in the diagnosis of advanced HIV infection]. / Utilidad de diferentes marcadores para el diagnóstico de la infección avanzada por el virus de la inmunodeficiencia humana.

BACKGROUND: The aim of this study was to evaluate the usefulness of different markers to diagnose advanced infection by the human immunodeficiency virus (HIV) (AIDS or CD4 lymphocyte < 0.2 x 10(9)/L), establish the degree of correlation and define markers of advanced infection in primary health care. METHODS: Clinical, hematological, biochemical, cellular, serological and immunological variables were analyzed in 146 patients diagnosed for the first time with HIV infection. The patients were classified into three stages: A (II, III, CDC-1987), B (IV-A, IV-C2) and C or advanced (IV-C1, IV-D). The following data were compared: the results in the three stages, the degree of correlation, the specificity and sensitivity to the diagnosis of AIDS. Two multiple logistic regression models were established: the first for all the variables and the second for only those available in primary health care. RESULTS: All the markers except the triglycerides, IgG, IgM, and beta 2-microglobulin presented significant differences in the stages (p < 0.05). With the exception of the CD3+, CD4+ and CD8+ lymphocytes (r > or = 0.6 or -0.6) the remaining variables were independent. The decrease in CD4+ and the increase in neopterin were very sensitive markers (> 95%) but only hyperamylasemia demonstrated a specificity greater than 95% for the diagnosis of advanced infection. Oropharyngeal candidiasis (OR = 4.80) and the CD4+ lymphocyte (OR = 0.99) had the greatest weight in the first model. In the second model the most significant markers were weight loss (OR = 4.41), a decrease in lymphocytes (OR = 7.65) and an increase in IgA (OR = 5.82) with p < 0.01 and a predictive value of 85.16%. CONCLUSIONS: The presence of weight loss, lymphocyte count < 1 x 10(9)/L and an increase in IgA may be used in primary health care to diagnose advanced infection by the human immunodeficiency virus. Asymptomatic hyperamylasemia with no apparent cause suggests advanced infection.

[Acute pancreatitis. A prospective epidemiological study in the province of Alicante. A Hospital Group for Study of Digestive Diseases in Alicante]. / Pancreatitis aguda. Estudio epidemiológico prospectivo en la provincia de Alicante. Grupo Hospitalario para el Estudio de Enfermedades Digestivas de Alicante.

OBJECTIVE: To gather epidemiological data on acute pancreatitis (AP) in Alicante area. EXPERIMENTAL DESIGN: A prospective study of patients admitted to all public hospitals with AP during 1991. PATIENTS: Patients over 14 years, with elevation of serum amylase and a consistent clinical presentation, or in whom AP was confirmed at laparotomy or postmortem. RESULTS: We identified 473 episodes of AP in 450 patients (236 males and 214 females). The mean age was 59.4 years. The annual incidence was 451 per million habitants/year. The commonest aetiology was biliary (52%) followed by idiopathic forms (24.7%), alcoholic (20.2%) and miscellaneous (2.9%). The overall mortality rate was 5.1%. Male were more frequently affected below 50 years of age (2.4 men/1 woman); the ratio being balanced above this age. Biliary etiology was more frequent in women, (63.5%), while alcoholic forms were more frequent in man (96.8%). 5.1% of patients presented more than one episode of AP during the year analysed. AP involved the 0.58% of the all patients admitted to the hospitals and the 0.14% of the all patients attended in hospital emergencies.

[Lipodystrophy and hyperglycemia produced by protease inhibitors]. / Lipodistrofia e hiperglucemia producidas por inhibidores de la proteasa.

BACKGROUND: HIV-1 protease inhibitors (PI) have been recently associated with a syndrome of anomalous body fat distribution or lipodystrophy (LD), which sometimes is associated to hyperglycemia. Many aspects of this syndrome remain obscure. The objective of the study is to describe the prevalence, clinical patterns, derangement of glucose metabolism associated and follow-up. METHODS: Patients taking at least one PI during January 1998 were asked a questionnaire about any body change, and a physical exam looking for fat changes was performed. In patients found to have LD, basal plasma glucose, cholesterol, triglycerides and cortisol were studied, and an oral glucose tolerance test (OGTT) was performed. In those cases with breast enlargement, prolactin and estradiol were measured. RESULTS: Among 272 patients, five cases (1.8%) of LD were detected. The syndrome appeared associated with all the IP available at the time of the study, a medium of 4.2 months after the introduction of the drug. The most common pattern was fat accumulation in abdomen and breast, and fat loss in arms, legs and face. Basal glycemia was normal in all 5 patients, but OGTT showed carbohydrate intolerance in two (both of them had family antecedents of type 2 diabetes mellitus). Only one patient need treatment withdrawal because of progressive deforming changes. CONCLUSIONS: The LD can appear in patients taking any IP. Body changes are usually self limited and in many patients PI don't need to be stopped.